On the down-regulation of cross-bridges occurring as changes in the cycling rate during tonic smooth muscle contractions.

As regards cross-bridge down-regulation, the following statements may summarize the results of our experiments: 1) The time course of cross-bridge down-regulation is the initial high turn-over rate followed by a continuous retardation without any distinct loss in force generation. These mechanisms allowed a rapid force development and an improvement in force maintenance. 2) Cross-bridge down-regulation was seen in the tracheal preparation of both the rat and the guinea pig. As indicated by the greater time constants of the post-vibration force recovery, the cross-bridge cycling rate seems to be distinctly lower in the guinea pig than in the rat trachea. 3) Cross-bridge down-regulation only occurs in smooth muscle preparations with intact cell membranes. This result would seem to hint that the sarcoplasmatic calcium concentration and/or the intactness of the cell membrane might be essential for producing cross-bridge down-regulation. 4) The recovery from cross-bridge down-regulation requires a rest period of more than 10s. The cross-bridges remain down-regulated during this time even after an increase in the sarcoplasmatic calcium concentration which was induced by a subsequent stimulus. This result indicates that changes in the sarcoplasmatic calcium cannot explain all the problems arising during cross-bridge down-regulation.

Re-acceleration of the down-regulated contraction kinetics in the rat tracheal smooth muscle.

The contraction kinetics of smooth muscle show a down-regulation after the transient rise found during sustained contraction. We tried to find out therefore if the contraction kinetics of rat tracheal smooth muscle can be re-accelerated during sustained activation. A 2 s length vibration (100 Hz sinusoidal; amplitude = 6% of the muscle length) produces an immediate fall in the force developed by the activated muscle. A biexponential function was fitted to the force recovery. The reciprocal of the time constant, t2, describing the slow component of force recovery, reflects the kinetics of contraction. The contraction kinetics reach their highest levels (t2 = 4.9 +/- 0.1 s,n = 166) about 30 s after the onset of electrical field stimulation. Three experimental groups were activated by either 10 microM serotonin (5-HT), 100 microM acetylcholine (ACh), or by 2 microM ACh for 50 min. Approximately 10 vibrations were applied to each preparation after an 8 min activation in order to observe stabilized down-regulated contraction kinetics. t2 values were calculated from the force recovery after vibration and averaged 11.2 +/- 0.2 s (n = 141), 11.5 +/- 0.2 s (n = 137), and 11.1 +/- 0.3 s (n = 84), respectively. After 50 min of continuous chemical activation, the preparation was stimulated additionally by the neurogenic release of acetylcholine. The t2 of post-vibration force recovery, as measured after 30 s of neural activation, showed no change in the specimens basically activated by 100 microM ACh (11.0 +/- 0.4 s, n = 51).(ABSTRACT TRUNCATED AT 250 WORDS)